Developmental Toxicity of the Dithiocarbamate Pesticide Sodium Metam in Zebrafish

Abstract

Sodium metam (NaM), a dithiocarbamate, is a general agricultural biocide applied prior to planting for the elimination of nematodes, soil pathogens, and weeds. There is a remarkable paucity of information about the mechanism of action and the risk that dithiocarbamates may pose to developing vertebrates. We have characterized NaM toxicity during early life stage exposure in zebrafish. Zebrafish embryos are most sensitive to NaM exposure during gastrulation and early segmentation (4-14 hours post fertilization, hpf). For mortality, the dose response curve is steep with an LC(50) estimate of 1.95 microM (248 ppb) at 48 hpf. The most notable malformation among surviving embryos was a severely twisted notochord, which became evident by 24 hpf. Surprisingly, this notochord defect was not immediately lethal and the animals continued to grow despite delays in hatching, apparent paralysis, and an inability to feed. We have characterized the notochord malformation using histological and in situ hybridization techniques. collagen 2a1 mRNA expression is normally localized to the notochord sheath cells at 24 hpf, whereas in NaM-exposed embryos it is misexpressed in the notochord cells. Histological staining and myoD expression indicate that the myotomes of the NaM-exposed embryos are less defined, compacted and block-shaped compared to controls. The degradation product of NaM, methyl isothiocyanate (MITC), causes similar malformations at similar concentrations as NaM, suggesting that MITC or another common product may be the active toxicant. Our results indicate that developing zebrafish are sensitive to NaM and MITC and we believe that this model is ideal to elucidate the molecular mechanism(s) and etiology of NaM toxicity in vertebrates.

Reproductive effects of prenatal exposure to nonylphenol on zebrafish (Danio rerio)

“…The primary causes emanated from the defects in axial structures during embryonic development. The possible role of pollutants in the aetiology of spinal deviations in fish has been discussed (Haya, 1989;Weis and Weis, 1989;Haendel et al, 2004). Most larvae with vertebral column flexure died after hatching or survived few days.…”

Developmental toxicity screening in zebrafish

“…All three milestones regularly are assessed and impacted in toxicology screens. For example, sodium metam (Haendel et al, 2004) and PFOS delayed the onset of spontaneous movement (Table 8). Embryos exposed to diethoxy CPO did not respond to touch (Jacobson et al, 2010).…”

Behavioral effects of low dissolved oxygen on the bivalve Macoma balthica

“…Where there was a significant effect of treatment, a Tukey's pair-wise multiple comparison test was performed. We plotted survival in each tank against the average DO, and analyzed it with a sigmoid least-squares regression and determined the LC 50 (relative to the Normoxic controls) in SigmaPlot (Version 8.02, SPSS Science, Chicago, IL; Haendel et al, 2004).…”